The induction of GSH synthesis by nanomolar concentrations of NO in endothelial cells: a role for γ-glutamylcysteine synthetase and γ-glutamyl transpeptidase

Nitric oxide protects cells from oxidative stress through a number of direct scavenging reactions with free radicals but the effects of nitric oxide on the regulation of antioxidant enzymes are only now emerging. Using bovine aortic endothelial cells as a model, we show that nitric oxide, at physiological rates of production (1–3 nM/s), is capable of inducing the synthesis of glutathione through a mechanism involving γ-glutamylcysteine synthetase and γ-glutamyl transpeptidase. This novel nitric oxide signalling pathway is cGMP-independent and we hypothesize that it makes an important contribution to the anti-atherosclerotic and antioxidant properties of nitric oxide.